Toxicological studies on delta 9-tetrahydrocannabinol (delta 9-THC) have revealed drug-induced changes in components of the reticulo- endothelial system. In the monkey, chronic intravenous (5-45-mg/kg) or oral (50-500 mg/kg) administration of delta 9-THC initiated a myeloid hyperplasia of bone marrow, thymus atrophy and leukocytosis (Thompson, Fleischman, Rosenkrantz and Braude, Toxicol. Appl. Pharmacol., in press). Similarly, rats chronically treated with large oral doses of delta 9-THC or crude marihuana extract exhibited hypocellularity of bone marrow and spleen (Thompson, Mason, Rosenkrantz and Braude, Toxicol. Appl. Pharmacol. 25: 373, 1973). More recently, with oral doses of delta 9-THC similar to those used by man, thymus atrophy and decreased total nucleated cells in bone marrow of rats were detected (Rosenkrantz, report to NIMH; MRI-MHOI-73-3). Since the thymus, spleen and bone marrow are major components of the reticule-endothelial system in the immune mechanisms, a study of the endogenous immune response capability of animals treated with delta 9-THC is paramount. It is proposed to perform a quantitative evaluation of the effects of delta 9-THC on the immune-defense systems. It is intended to assess the inductive and productive phases of the primary and secondary humoral antibody responses. The primary immune response will be evaluated by challenging different groups of rats with sheep red blood cells (particulate antigen) before, during or after subacute treatment with delta 9-THC or vehicle. The secondary immune response will be assessed in other groups of rats treated initialy with the particulate antigen and presented a second dose of antigen several weeks later in conjunction with or without drug treatment. In both studies, humoral antibody will be quantitated by the hemagglutinin and Jerne plague-forming antibody cell techniques.